In the discussion that follows, reference is made to certain structures and/or methods. However, the following references should not be construed as an admission that these structures and/or methods constitute prior art. Applicants expressly reserve the right to demonstrate that such structures and/or methods do not qualify as prior art.
Many RNA viruses, including Yellow Fever (YF) virus and Venezuelan Equine Encephalitis (VEE) virus, are dangerous human pathogens. VEE is a Category B and YF is a Category C Priority Pathogen as categorized by NIH/NIAID.
The VEE virus is a positive single-stranded RNA arbovirus that belongs to the Alphavirus genus of the Togaviridae family. The virus is transmitted primarily by mosquitoes, which bite an infected animal and then bite and feed on another animal or human. VEE currently is rare in the U.S. A major epizootic in horses occurred in Texas, but only about 100 laboratory-confirmed cases in humans have been documented. However, changing climate may favor establishment of the virus in wanner areas of the U.S. Additionally, VEE is a potential biological weapon and bioterrorism agent.
The YF virus is also a positive single-stranded RNA arbovirus. However, unlike VEE, the YF virus belongs to the family Flaviviridae. YF disease occurs mostly in Africa and South America. Human infection begins after deposition of viral particles through the skin by an infected mosquito. The disease is frequently severe. More moderate cases can occur as a result of previous infection by another flavivirus. There is a difference between disease outbreaks in rural or forest areas and in urban areas (Barnett, 2007). Disease outbreaks in towns and non-native people can be more serious because of higher densities of mosquito vectors and higher population densities. As of 2001, the World Health Organization (WHO) estimates that YF virus causes 200,000 illnesses and 30,000 deaths every year in unvaccinated populations. In most cases, supportive therapy is required for YF patients. Fluid replacement, transfusion of blood derivates, and other measures are used in severe cases.
Live attenuated viruses have been developed to serve as vaccines for many RNA viruses such as VEE and YF, poliomyelitis, influenza, measles, mumps, rabies, and rubella viruses. Traditional live attenuated RNA virus vaccines comprise live attenuated RNA viruses that are injected into the vaccine recipient. The injected virus delivers its RNA genome into the cells, which results in production of viral antigens as well as progeny attenuated viruses in the tissues of the vaccine recipient. This leads to the elicitation of an immune response that protects against the counterpart non-attenuated virus.